It is proposed to continue biochemical studies of parasitic helminths which have been inaugurated over the previous five years of this proposal (AI09483). Particular emphasis will be placed upon the energy metabolisms of the intestinal nematode Ascaris lumbricoides var. suum and the intestinal cestode Hymenolepis diminuta. A number of striking differences have become apparent between the host and parasite metabolisms. These differences have been shown to exist at the level of overall metabolic pathways as well as at the more subtle level of enzyme kinetics and structure. More recently, the importance of differences in enzyme distribution within the tissues and cellular organelles have become increasingly apparent. Such differences have been shown to be vulnerable to chemotherapeutic attack. Detailed metabolic studies of the parasitic helminths will continue in an effort to attain a more precise appreciation of the comparative aspects of host and parasite biochemistry which, in turn, is essential for a more basic understanding of host-parasite and parasite-drug interactions. Specific areas of investigation will inclue: a) the mechanisms of formation of succinate and volatile fatty acids by adult Ascaris, b) comparative studies of the reactions and functioning of anaerobic Ascaris and Hymenolepis mitochondria which are quite different from the corresponding mammalian structures, c) the mode of action of anthelmintics upon energy producing mitochondrial reactions in the parasites.